Lurasidone is an atypical antipsychotic developed by Dainippon Sumitomo Pharma for the treatment of Schizophrenia and bipolar disorders.
Lurasidone HCl is chemically known as (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione hydrochloride.
Lurasidone hydrochloride and the processes for its preparation are disclosed in U.S. Pat. No. 5,532,372. While several organic and inorganic acids are mentioned as possible salt-forming agents, including hydrochloric acid, there is no mention of particular dihydrochloride salt which is the subject of the present application.
The marketed product, Latuda, is the monohydrochloride salt described above. Lurasidone hydrochloride is very slightly soluble in water, practically insoluble in 0.1 N HCl hence having poor bioavailability of less than 12%. For development of pharmaceutical formulations, particularly oral dosage forms, the active ingredient must have sufficient oral bioavailability. There is a demand in the art for a new Lurasidone salt, which would be more soluble, stable with remarkable pharmacokinetic properties and more suitable for technological processing, than hydrochloride salt which is used in the marketed pharmaceutical formulations.
These alternative salts and salt forms must also pass the quality and safety criteria set out by the various health authorities worldwide and can themselves be marketed as equally efficacious and often more cost effective alternatives to patient groups and healthcare services.
The formation of salts of Lurasidone with the desired advantageous properties has proved to be difficult. The inventors have succeeded in preparing novel Lurasidone salt and different forms of said novel salt. Extensive research has shown that the salts of Lurasidone according to the invention have proved to be that possess high water solubility particularly compared with the hydrochloride salt forms of Lurasidone and its free base. The water solubility of the new Lurasidone salts and hydrates makes the new compounds particularly suitable for human consumption.